Review: History of the amyloid fibril

Rudolph Virchow, in 1854, introduced and popularized the term amyloid to de note a macroscopic tissue abnormality that exhibited a positive iodine stai ning reaction. Subsequent light microscopic studies with polarizing optics demonstrated the inherent birefringence of amyloid deposits, a property tha t increased intensely after staining with Congo red dye. In 1959, electron microscopic examination of ultrathin sections of amyloidotic tissues reveal ed the presence of fibrils, indeterminate in length and, invariably, 80 to 100 Angstrom in width. Using the criteria of Congophilia and fibrillar morp hology, 20 or more biochemically distinct forms of amyloid have been identi fied throughout the animal kingdom; each is specifically associated with a unique clinical syndrome. Fibrils, also 80 to 100 A in width, have been iso lated from tissue homogenates using differential sedimentation or solubilit y. X-ray diffraction analysis revealed the fibrils to be ordered in the bet a pleated sheet conformation, with the direction of the polypeptide backbon e perpendicular to the fibril axis (cross beta structure). Because of the s imilar dimensions and tinctorial properties of the fibrils extracted from a myloid-laden tissues and amyloid fibrils in tissue sections, they have been assumed to be identical. However, the spatial relationship of proteoglycan s and amyloid P component (AP), common to all forms of amyloid, to the puta tive protein only fibrils in tissues, has been unclear. Recently, it has be en suggested that, in situ, amyloid fibrils are composed of proteoglycans a nd AP as well as amyloid proteins and thus resemble connective tissue micro fibrils. Chemical and physical definition of the fibrils in tissues will be needed to relate the in vitro properties of amyloid protein fibrils to the pathogenesis of amyloid fibril formation in vivo. (C) 2000 Academic Press.